Metabolic capacity for l-citrulline synthesis from ammonia in rat isolated colonocytes

Mouillé, Béatrice; Morel, Éric; Robert, Véronique; G, Guihot-Joubrel; Blachier, François

doi:10.1016/s0304-4165(99)00045-8

Cited by 25 publications

(15 citation statements)

References 23 publications

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“…An effect of ammonia on cell respiration through the depletion of ␣-ketoglutarate in the tricarboxylic cycle can be excluded since in previous experiments, NH 4 Cl did not modify ␣-ketoglutarate oxidation in rat colonocytes (41). In gastric mucosal cells, Tsujii and al.…”

Section: Discussionmentioning

confidence: 89%

Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet

Andriamihaja

Davila

Eklou-Lawson

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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112

107

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Hyperproteic diets are used in human nutrition to obtain body weight reduction. Although increased protein ingestion results in an increased transfer of proteins from the small to the large intestine, there is little information on the consequences of the use of such diets on the composition of large intestine content and on epithelial cell morphology and metabolism. Rats were fed for 15 days with either a normoproteic (NP, 14% protein) or a hyperproteic isocaloric diet (HP, 53% protein), and absorptive colonocytes were observed by electron microscopy or isolated for enzyme activity studies. The colonic luminal content was recovered for biochemical analysis. Absorbing colonocytes were characterized by a 1.7-fold reduction in the height of the brush-border membranes (P = 0.0001) after HP diet consumption when compared with NP. This coincided in the whole colon content of HP animals with a 1.8-fold higher mass content (P = 0.0020), a 2.2-fold higher water content (P = 0.0240), a 5.2-fold higher protease activity (P = 0.0104), a 5.5-fold higher ammonia content (P = 0.0008), and a more than twofold higher propionate, valerate, isobutyrate, and isovalerate content (P < 0.05). The basal oxygen consumption of colonocytes was similar in the NP and HP groups, but ammonia was found to provoke a dose-dependent decrease of oxygen consumption in the isolated absorbing colonocytes. The activity of glutamine synthetase (which condenses ammonia and glutamate) was found to be much higher in colonocytes than in small intestine enterocytes and was 1.6-fold higher (P = 0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity remained unchanged. Thus hyperproteic diet ingestion causes marked changes both in the luminal environment of colonocytes and in the characteristics of these cells, demonstrating that hyperproteic diet interferes with colonocyte metabolism and morphology. Possible causal relationships between energy metabolism, reduced height of colonocyte brush-border membranes, and reduced water absorption are discussed.

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Section: Discussionmentioning

confidence: 89%

Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet

Andriamihaja

Davila

Eklou-Lawson

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

112

107

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“…We previously demonstrated (25) in colonocytes the metabolic capacity for an incomplete ornithine cycle, acting as a probable detoxification pathway against ammonia. In these cells, the direct conversion of L-arginine into L-citrulline and nitric oxide through nitric oxide synthase activity is negligible when compared with the sequential conversion of L-arginine into L-citrulline through arginase and OCT activities (25,28).…”

Section: Discussionmentioning

confidence: 99%

“…In these cells, the direct conversion of L-arginine into L-citrulline and nitric oxide through nitric oxide synthase activity is negligible when compared with the sequential conversion of L-arginine into L-citrulline through arginase and OCT activities (25,28). The already described adaptation of the hepatic urea cycle enzymes to an increased protein intake led us to study colonic epithelial cell metabolism in response to increased luminal ammonia concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Carbamoyl phosphate (carbamoyl-P) synthesized by the intramitochon-drial carbamoyl-P synthetase I (CPSI) is channeled through ornithine carbamoytransferase (OCT), which combines this metabolite with L-ornithine to form L-citrulline. Incorporation of ammonia into L-citrulline by the colon epithelial cells may correspond to a first line of defense against luminal NH 4 ϩ /NH 3 entry into the bloodstream (25).…”

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confidence: 99%

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Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion

Mouillé¹,

Robert²,

Blachier³

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Mouillé, Béatrice, Véronique Robert, and François Blachier. Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion. Am J Physiol Gastrointest Liver Physiol 287: G344 -G351, 2004. First published April 2, 2004 10.1152/ajpgi.00445.2003.-Chronic highprotein consumption leads to increased concentrations of NH4 ϩ /NH3 in the colon lumen. We asked whether this increase has consequences on colonic epithelial cell metabolism. Rats were fed isocaloric diets containing 20 (P20) or 58% (P58) casein as the protein source for 7 days. NH4 ϩ /NH3 concentration in the colonic lumen and in the colonic vein blood as well as ammonia metabolism by isolated surface colonic epithelial cells was determined. After 2 days of consumption of the P58 diet, marked increases of luminal and colonic vein blood NH4 ϩ /NH3 concentrations were recorded when compared with the values obtained in the P20 group. Colonocytes recovered from the P58 group were characterized at that time and thereafter by an increased capacity for L-ornithine and urea production through arginase (P Ͻ 0.05). L-Ornithine was mostly used in the presence of NH4Cl for the synthesis of the metabolic end product L-citrulline. After 7 days of the P58 diet consumption, however, the ammonia metabolism into Lcitrulline was found lower (P Ͻ 0.01) when compared with the values measured in the colonocytes recovered from the P20 group despite any decrease in the related enzymatic activities (i.e., carbamoylphosphate synthetase I and ornithine carbamoyl transferase). This decrease was found to coincide with a return of blood NH4 ϩ /NH3 concentration in colonic portal blood to values close to the one recorded in the P20 group. In response to increased NH 4 ϩ /NH3 concentration in the colon, the increased capacity of the colonocytes to synthesize L-ornithine is likely to correspond to an elevated Lornithine requirement for the elimination of excessive blood ammonia in the liver urea cycle. Moreover, in the presence of NH 4Cl, colonocytes diminished their synthesis capacity of L-citrulline from Lornithine, allowing a lower cellular utilization of this latter amino acid. These results are discussed in relationship with an adaptative process that would be related to both interorgan metabolism and to the role of the colonic epithelium as a first line of defense toward luminal NH 4 ϩ /NH3 concentrations.

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“…Several AA-derived bacterial metabolites are metabolic troublemakers in IEC, namely H 2 S, p -cresol, and ammonia [64,65,66]. The inhibition of mitochondrial respiration induced by p -cresol is associated with an increase in superoxide anion production in IEC, probably implicated in the genotoxicity of this compound [64].…”

Section: Potential Role Of Dietary Proteins In Inflammatory Flarementioning

confidence: 99%

Dietary Protein and Amino Acid Supplementation in Inflammatory Bowel Disease Course: What Impact on the Colonic Mucosa?

et al. 2017

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Inflammatory bowel diseases (IBD), after disease onset, typically progress in two cyclically repeated phases, namely inflammatory flare and remission, with possible nutritional status impairment. Some evidence, either from epidemiological, clinical, and experimental studies indicate that the quantity and the quality of dietary protein consumption and amino acid supplementation may differently influence the IBD course according to the disease phases. For instance, although the dietary protein needs for mucosal healing after an inflammatory episode remain undetermined, there is evidence that amino acids derived from dietary proteins display beneficial effects on this process, serving as building blocks for macromolecule synthesis in the wounded mucosal area, energy substrates, and/or precursors of bioactive metabolites. However, an excessive amount of dietary proteins may result in an increased intestinal production of potentially deleterious bacterial metabolites. This could possibly affect epithelial repair as several of these bacterial metabolites are known to inhibit colonic epithelial cell respiration, cell proliferation, and/or to affect barrier function. In this review, we present the available evidence about the impact of the amount of dietary proteins and supplementary amino acids on IBD onset and progression, with a focus on the effects reported in the colon.

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Metabolic capacity for l-citrulline synthesis from ammonia in rat isolated colonocytes

Cited by 25 publications

References 23 publications

Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet

Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet

Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion

Dietary Protein and Amino Acid Supplementation in Inflammatory Bowel Disease Course: What Impact on the Colonic Mucosa?

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